ALZHEIMER'S DEMENTIA

Dementia is a loss of brain function that occurs with certain diseases. Alzheimer's disease (AD), is one form of dementia that gradually gets worse over time. It affects memory, thinking, and behavior.

Memory impairment, as well as problems with language, decision-making ability, judgment, and personality, are necessary features for the diagnosis.

Causes, incidence, and risk factors:

Age and family history are risk factors for AD.

• As you get older, yoru risk of developing AD goes up. However, developing Alzheimer's disease is not a part of normal aging.
• Having a close blood relative, such as a brother, sister, or parent who developed AD increases your risk.
• Having certain combination of genes for proteins that appear to be abnormal in Alzheimer's disease also increases your risk.

Other risk factors that are not as well proven include:

• Longstanding high blood pressure
• History of head trauma
• Female gender

There are two types of AD -- early onset and late onset.

• In early onset AD, symptoms first appear before age 60. Early onset AD is much less common than late onset. However, it tends to progress rapidly. Early onset disease can run in families. Several genes have been identified.
• Late onset AD, the most common form of the disease, develops in people age 60 and older. Late onset AD may run in some families, but the role of genes is less clear.

The cause of AD is not entirely known, but is thought to include both genetic and environmental factors. A diagnosis of AD is made when certain symptoms are present, and by making sure other causes of dementia are not present.

The only way to know for certain that someone has AD is to examine a sample of their brain tissue after death. The following changes are more common in the brain tissue of people with AD:

• "Neurofibrillary tangles" (twisted fragments of protein within nerve cells that clog up the cell)
• "Neuritic plaques" (abnormal clusters of dead and dying nerve cells, other brain cells, and protein)
• "Senile plaques" (areas where products of dying nerve cells have accumulated around protein).

Alzheimer's disease

When nerve cells (neurons) are destroyed, there is a decrease in the chemicals that help nerve cells send messages to one another (called neurotransmitters). As a result, areas of the brain that normally work together become disconnected.

The buildup of aluminum, lead, mercury, and other substances in the brain is no longer believed to be a cause of AD.

treatment:

 None of the available treatments for Alzheimer's dementia are curative or are known to reverse or halt the process of the disease. The primary goal of treatment is to maintain cognitive function and to improve quality of life for the patient. A thorough baseline assessment using rating scales (eg, mini-mental status exam, global deterioration scale) should be performed before starting drug therapy. Dose titration should be done slowly in order to assess the tolerability of the regimen and to minimize the incidence of severe adverse drug reactions.
Cholinesterase inhibitors (eg, donepezil, rivastigmine, galantamine, tacrine):                                 

Although the etiology of cognitive impairment in Alzheimer's disease is not fully understood, it has been reported that acetylcholine-producing neurons degenerate in the brains of patients with Alzheimer's disease. It is believed that AChE inhibitors exert their effects by enhancing cholinergic function. This is accomplished by increasing the concentration of acetylcholine through reversible inhibition of its hydrolysis by cholinesterase. These agents can be classified as non-selective (eg, tacrine) or selective (eg, donepezil) reversible inhibitors of AChE. Tacrine is a potent centrally-acting inhibitor of AChE. However, it is used infrequently in clinical practice due to side effects that are often significant and dose-limiting (eg, hepatotoxicity, GI upset). Selective inhibitors of AChE in the CNS have improved safety profiles since they have little effect on AChE in the peripheral tissues; these agents are not associated with hepatotoxicity. 

These drugs may be used to aid in improving cognitive functioning or to slow disease progression in mild-moderate Alzheimer's dementia. A decrease in the frequency of behavioral and neuropsychiatric symptoms may be another benefit. An observation period of 6 to 12 months is necessary to assess the efficacy of the therapeutic regimen. Therapy should be discontinued when continued or accelerated deterioration is seen after 6 months' therapy. Switching to an alternative cholinesterase inhibitor is recommended if the MMSE score is greater than 2 to 4 points after a year of treatment.
N-methyl-D-aspartate receptor antagonists (eg, memantine):                                                        

Persistent activation of N-methyl-D-aspartate (NMDA) receptors in the CNS by the excitatory amino acid glutamate is believed to contribute to the symptoms of Alzheimer’s disease. Memantine is believed to exert its therapeutic effect through its action as a low to moderate affinity uncompetitive (open-channel) NMDA receptor antagonist which binds preferentially to the NMDA receptor-operated cation channels.

Memantine is indicated for moderate to severe Alzheimer's dementia, either as monotherapy or in combination with cholinesterase inhibitors; it has not been shown to prevent or slow neurodegeneration.